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Updated: Nov 25, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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Centrosomal Localization of RXRα Promotes PLK1 Activation and Mitotic Progression and Constitutes a Tumor

Guobin Xie1, Yuqi Zhou2, Xuhuang Tu1

  • 1School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, Fujian, China.

Developmental Cell
|December 15, 2020
PubMed

Insights

Retinoid X receptor alpha (RXRα) is phosphorylated during mitosis, interacting with PLK1 at the centrosome to promote cell division. This interaction is elevated in tumors, offering a new target for cancer drug development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Retinoid X receptor alpha (RXRα) is a nuclear receptor regulating cellular processes.
  • Mitosis involves complex protein interactions crucial for cell division.

Purpose of the Study:

  • To investigate the role of RXRα during mitosis.
  • To identify novel therapeutic targets in cancer based on RXRα function.

Main Methods:

  • Phosphorylation site identification of RXRα.
  • Analysis of RXRα interaction with PLK1 at the centrosome.
  • In vivo and in vitro cancer models were used.

Main Results:

  • RXRα is phosphorylated by Cdk1 at mitosis onset, translocating to the centrosome.
  • Phosphorylated RXRα (p-RXRα) interacts with PLK1, promoting centrosome maturation and mitotic progression.
  • Elevated p-RXRα levels are observed in cancer cell lines, animal carcinogenesis, and human tumors.
  • A specific RXRα ligand, XS060, inhibits p-RXRα/PLK1 interaction, causing tumor-specific mitotic arrest.

Conclusions:

  • RXRα has a transcription-independent role at the centrosome during mitosis.
  • p-RXRα represents a tumor-specific vulnerability for developing novel mitotic drugs.
  • Targeting the p-RXRα/PLK1 interaction offers a promising therapeutic strategy with an improved therapeutic index.
Keywords:
Cdk1PLK1RXRαRXRα ligandRXRα phosphorylationcatastrophecentrosomemitosisnuclear receptortumor vulnerability

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